The incidence of obesity and a cluster of disorders associated with obesity such as type 2 diabetes, hepatosteatosis, dyslipidemia and cardiovascular disease have risen to alarming proportions and there is great need for effective therapeutic and preventive measures against these health threats. Metabolic disorders often affect an intertwined network of signaling and metabolic pathways and it is crucial to understand the interactions of these pathways in a patient-specific setting for drug target discovery and therapy development. We have recently identified a number of long noncoding RNAs (lncRNAs) that regulate critical aspects of glucose and lipid metabolism in healthy and diseased mice and could potentially play important pathological roles in human disorder. Using CRISPR technology, we are producing iPS cells carrying loss-of-function mutations for these lncRNAs and are differentiating them into metabolic cells and investigating their potentials in human metabolic disease.